FDA Patient Safety News: Show #25, March 2004

New Lab Test for Anthrax

FDA recently cleared for marketing a new test kit that will make it easier for laboratories to distinguish Bacillus anthracis, the organism that causes anthrax disease, from other Bacillus types. The test kit, manufactured by Tetracore, Incorporated, is called Redline Alert. It's an immunoassay that contains a monoclonal antibody which binds to a surface protein found on the anthrax bacillus.

A positive result with Redline Alert is presumptive evidence of infection with the anthrax bacillus, but confirmatory tests are needed to make a definitive identification of the organism. This means that laboratories must use a combination of methods and testing to definitively identify or rule out an anthrax infection.

Redline Alert is only intended to be performed on bacterial colonies grown from clinical specimens, and they must be grown on sheep blood agar plates. Once the cells are growing in the lab cultures, the test can be performed in about 15 minutes.

The test cannot be used to identify the anthrax organism in suspicious materials such as packages or powders. Also, this test should only be used by labs whose staffs are trained and proficient with microbiological culture procedures and who use Biological Safety Level 2 practices.

Keep in mind, too, that CDC recommends consulting with your state public health laboratory director whenever you suspect infection with Bacillus anthracis.

Additional Information:

CDC. Laboratory Procedures for Identification of Bacillus anthracis.

http://www.bt.cdc.gov/agent/anthrax/LevelAProtocol/anthraxlabprotocol.pdf


Warning on Metabolic Acidosis with Topamax

Ortho-McNeil Pharmaceuticals has revised the prescribing information for the antiepileptic drug Topamax (topiramate) to include a warning that the drug causes hyperchloremic metabolic acidosis.

In many patients, the only sign of this is decreased serum bicarbonate. But in some patients, metabolic acidosis can result in hyperventilation, non-specific symptoms such as fatigue and anorexia, or more severe sequelae such as cardiac arrhythmias or stupor. If left untreated, chronic metabolic acidosis can lead to kidney stones, skeletal problems with an increased risk of fractures, and decreased growth in children.

In clinical trials where Topamax was used as an adjunct treatment for epilepsy in adults and children, significantly more patients on the drug had persistently decreased serum bicarbonate levels than those treated with placebo. Decreases in serum bicarbonate generally occur soon after treatment is started, but they can occur at any time during treatment. Also, the decrease in bicarbonate can occur at doses as low as 50 mg per day. The bicarbonate lowering effect of Topamax can be made worse by certain drugs, or by conditions that predispose patients to acidosis. These include renal disease, severe respiratory disorders, a ketogenic diet, and diarrhea.

The new labeling recommends measuring serum bicarbonate levels at baseline, and then periodically during a patient's Topamax treatment. If metabolic acidosis develops and persists, consider reducing the dose or gradually discontinuing the drug. If a patient with persistent acidosis continues on Topamax, consider alkali treatment.

Additional Information:

FDA MedWatch Safety Alert - Topamax (topiramate) Tablets/Sprinkle Capsules.
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm169486.htm


Caution on Treating Infants with Tamiflu

Roche Laboratories has cautioned health care professionals about using the flu drug Tamiflu in infants under one year of age. Tamiflu, or oseltamivir phosphate, is approved to treat influenza in patients one year and older. It's also indicated for flu prophylaxis in adults and adolescents 13 and older. However, it's not indicated for either flu treatment or prophylaxis in infants under one year.

New preclinical safety data from animal studies have shown high drug exposure in the brains of very young animals. The company says that these high exposures may be related to an immature blood-brain barrier. Although the clinical significance of these findings is uncertain, Roche recommends that Tamiflu not be given to children younger than 1 year - that is, before the blood-brain barrier is thought to be fully developed. The company also emphasizes the importance of using Tamiflu only for the labeled indications.

Additional Information:

FDA Medwatch Safety Alert - Tamiflu (oseltamivir phosphate) Capsules and for Oral Suspension.
http://www.fda.gov/Safety/MedWatch/SafetyInformation/Safety-RelatedDrugLabelingChanges/ucm111024.htm


Warning about Extreme Sleepiness with Permax

Here's a new warning about the dopamine agonist Permax (pergolide mesylate). Eli Lilly, the manufacturer, says that patients treated with Permax have reported falling asleep while performing daily activities, including driving. Some of these events led to accidents.

Although many of these patients reported previous somnolence while on Permax, some said they had no warning signs, such as excessive drowsiness, and they recall being alert immediately before the event. Some of these events occurred as late as one year after starting treatment. And so the drug's labeling now says that prescribers should continually reassess their patients for drowsiness or sleepiness while they're being treated with Permax, especially since some of these events can occur well after the start of treatment. And it points out that patients may not mention drowsiness or sleepiness until they're questioned directly about whether they experience somnolence during specific activities.

Before starting treatment with Permax, Lilly says that patients should be told about the potential for drowsiness during daily activities, and specifically asked about factors that may increase this risk, such as whether they're using other sedating medications or whether they have a sleep disorder.

Patients should also be cautioned about operating hazardous machinery, including automobiles, until they're reasonably sure that Permax doesn't cause them to be drowsy. And they should be told that if drowsiness or episodes of falling asleep increase at any time during treatment, they shouldn't drive or participate in other potentially dangerous activities until they've contacted their physician. If a patient does develop significant daytime sleepiness, or if they fall asleep during activities that require participation, the company says that Permax should ordinarily be discontinued. If the medication is continued, patients should be advised not to drive and to avoid other potentially dangerous activities.

Additional Information:

FDA MedWatch Safety Alert - Permax (pergolide mesylate).
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm152695.htm


More on Dangerous Abbreviations

In previous broadcasts, we've talked about the ways that abbreviations can cause medication errors. Although abbreviations and other symbols can save time, they aren't always read correctly, and they can be interpreted differently by different practitioners.

The Institute for Safe Medication Practices recently published an updated list of some of the most error-prone abbreviations and dose designations. ISMP identifies dozens of dangerous abbreviations, including the prohibited abbreviations that are a part of JCAHO's National Patient Safety Goals for 2004. Let's take a look at the items on JCAHO's "do not use" list.

First, the abbreviations "U" and "IU". The "U" can easily be mistaken as the number "0", particularly when the "U" is written too closely after the number. This can lead to tenfold overdoses. And "IU" can be mistaken for "IV" or the number "10". So instead of using "U" and "IU", use the terms "unit" and "international unit".

Next, there's "q.d.", meaning every day, and "q.o.d.", meaning every other day. "q.d." can be mistaken as "q.i.d.", especially if the period after the "q" or the tail of the "q" is misunderstood as an "i". And "q.o.d." can be mistaken for "q.d." or "q.i.d." if the "o" is poorly written. Instead, write out "daily" or "every other day".

Then there's the possible confusion with dose designations that include decimal points. A trailing zero after a decimal point can make a "1.0 mg" dose look like a 10 mg dose if the decimal point isn't seen. Similarly, ".5 mg" can look like "5 mg". So don't use trailing zeros for doses expressed in whole numbers and be sure to use a leading zero when the dose is less than a whole unit.

Finally, the confusion between the abbreviations for magnesium sulfate (MgSO4) and morphine sulfate (MSO4 or MS), which can look similar or be misinterpreted. Here, write out "magnesium sulfate" or "morphine sulfate". The ISMP list has many more examples of potentially dangerous abbreviations.

Additional Information:

ISMP List of Error-Prone Abbeviations, Symbols and Dose Designations. November 27, 2003.

http://www.ismp.org/PDF/ISMPAbbreviations.pdf


FDA Decision on Silicone Gel-filled Breast Implants

Your patients may be asking about FDA's recent decision to turn down a manufacturer's application to market silicone gel-filled breast implants. Women may want to know why FDA did this, what the decision means in terms of safety, what kinds of implants remain available and under what circumstances, and what the future holds.

After reviewing the manufacturer's application for marketing, FDA decided that it didn't contain sufficient data to establish the safety profile for this device. FDA was particularly concerned that there wasn't enough information about the long-term performance of these implants in actual use. For example, at what rate do they rupture, what causes rupture, and how long do the implants remain intact before rupture takes place? Also, more information is needed about the silicone that leaches out of the implant over time. Without this information, FDA cannot decide whether there's a reasonable assurance that the implants are safe and effective.

FDA’s decision not to approve the implants doesn’t mean that FDA believes they’re unsafe, and that's an important point to keep in mind for women who have these implants. It means that there isn't enough information right now to give women and their physicians an accurate picture of how these devices will perform and what the various risks might be.

Performing the research to get this information is the responsibility of the manufacturer who wants to market the implants. FDA is helping in this process by updating its guidance for breast implant manufacturers. This guidance spells out in detail the kinds of data FDA will need to make a determination on safety and effectiveness. It's now up to manufacturers to use the guidance to develop this information, and then submit it to FDA.

In the meantime, women who want breast implants have several options. First of all, saline-filled implants continue to be available without restriction. And there are two circumstances where the silicone gel-filled implants are available. First, a woman who wants the implants for breast reconstruction-for example, after mastectomy-or to replace an existing implant, can still get them by having her surgeon enroll her in a clinical study. Also, a limited number of women who want the silicone gel-filled implants for breast augmentation may be able to get them by enrolling in studies that may be conducted by the implant manufacturer based on FDA's updated guidelines.

Additional Information:

FDA/CDRH – Breast Implants.
http://www.fda.gov/cdrh/breastimplants/


FDA Decision on Silicone Gel-filled Breast Implants

Your patients may be asking about FDA's recent decision to turn down a manufacturer's application to market silicone gel-filled breast implants. Women may want to know why FDA did this, what the decision means in terms of safety, what kinds of implants remain available and under what circumstances, and what the future holds.

After reviewing the manufacturer's application for marketing, FDA decided that it didn't contain sufficient data to establish the safety profile for this device. FDA was particularly concerned that there wasn't enough information about the long-term performance of these implants in actual use. For example, at what rate do they rupture, what causes rupture, and how long do the implants remain intact before rupture takes place? Also, more information is needed about the silicone that leaches out of the implant over time. Without this information, FDA cannot decide whether there's a reasonable assurance that the implants are safe and effective.

FDA’s decision not to approve the implants doesn’t mean that FDA believes they’re unsafe, and that's an important point to keep in mind for women who have these implants. It means that there isn't enough information right now to give women and their physicians an accurate picture of how these devices will perform and what the various risks might be.

Performing the research to get this information is the responsibility of the manufacturer who wants to market the implants. FDA is helping in this process by updating its guidance for breast implant manufacturers. This guidance spells out in detail the kinds of data FDA will need to make a determination on safety and effectiveness. It's now up to manufacturers to use the guidance to develop this information, and then submit it to FDA.

In the meantime, women who want breast implants have several options. First of all, saline-filled implants continue to be available without restriction. And there are two circumstances where the silicone gel-filled implants are available. First, a woman who wants the implants for breast reconstruction-for example, after mastectomy-or to replace an existing implant, can still get them by having her surgeon enroll her in a clinical study. Also, a limited number of women who want the silicone gel-filled implants for breast augmentation may be able to get them by enrolling in studies that may be conducted by the implant manufacturer based on FDA's updated guidelines.

Additional Information:

FDA Press Release: FDA Provides Pathway for Sponsors Seeking Approval of Breast Implants.
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2004/ucm108222.htm



FDA Patient Safety News is available at www.fda.gov/psn